Xanthine oxidase is an enzyme catalyzing the conversion of hypoxanthine to xanthine and further to uric acid in nucleic acid metabolism.
A xanthine oxidase inhibitor inhibits uric acid synthesis to reduce a level of uric acid in the blood with respect to the action of xanthine oxidase. That is, a xanthine oxidase inhibitor is effective as a therapeutic agent for hyperuricemia and various diseases caused by hyperuricemia. On the other hand, there are gouty arthritis and gouty tophus called gout as a clinical condition caused as a result of deposition of urate crystals after prolonged hyperuricemia. In addition, hyperuricemia is considered to be important as a factor of lifestyle diseases associated with obesity, hypertension, dyslipidemia and diabetes or metabolic syndromes, and recently, it has been clarified that hyperuricemia is a risk factor of renal damage, urinary calculi and cardiovascular diseases according to epidemiological surveys (Guideline for the Management of Hyperuricemia and Gout, 2nd edition). Further, a xanthine oxidase inhibitor is expected to be useful for the treatment of diseases associated with active oxygen species by the active oxygen species generation inhibitory activity, for example, for the treatment of cardiovascular diseases through the vascular function-improving action (Circulation. 2006; 114: 2508-2516).
Allopurinol and febuxostat are clinically used as a therapeutic agent for hyperuricemia, but allopurinol has been reported to have a side effect such as Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic disorder and renal dysfunction (Nippon Rinsho, 2003; 61, Suppl. 1: 197-201).
As a compound having a xanthine oxidase inhibitory activity, for example, there have been reported a phenyl pyrazole derivative (Patent Documents 1 to 3), and a triaryl carboxylic acid derivative (Patent Documents 4 to 7), and the like, such as a pyrazole derivative in which the central aromatic ring is a benzene ring. In addition, there has been reported a pyrazole derivative which is a central bicyclic hetero ring such as a 6-indolepyrazole derivative (Patent Documents 8).
On the other hand, in Non-Patent Documents 1 and 2, a pyrazole carboxylic acid derivative having a pyridine ring in the center is reported.